Réaction #1576

Équation de réaction

propargylamine

5'-amino-4'-chloro-2'-fluoroacetanilide

triethylamine

phenylchloroformate

→

title product

1-(5-Acetamido-2-chloro-4-fluorophenyl)-3-(2-propynyl)urea

Solvants

tetrahydrofuran

water

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Températurewhile maintaining the reaction mixture temperature at 25°-30° C
2. 2
   workup.ADDITIONAfter the addition
3. 3
   LavageThe organic mixture is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine
4. 4
   Séchagedried over anhydrous magnesium sulfate
5. 5
   Concentrationconcentrated in vacuo
6. 6
   Autreto obtain a tan solid
7. 7
   Températurerefluxed for 1 hour
8. 8
   FiltrationThe aqueous mixture is filtered
9. 9
   Autreto obtain a solid which
10. 10
    Lavageis washed sequentially with water, 0.5N hydrochloric acid and water
11. 11
    Autredried overnight

Mode opératoire

A solution of 5'-amino-4'-chloro-2'-fluoroacetanilide (11.25 g, 55.6 mmol), and triethylamine (7.70 mL, 55.6 mmol) in tetrahydrofuran is added dropwise to a stirred solution of phenylchloroformate (8.70 mL, 69.4 mmol) in tetrahydrofuran while maintaining the reaction mixture temperature at 25°-30° C. After the addition is complete, the reaction mixture is stirred at room temperature for 75 minutes, and poured into ethyl acetate. The organic mixture is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain a tan solid. A solution of the solid in tetrahydrofuran is treated with propargylamine (9.52 mL, 139 mmol), refluxed for 1 hour, and poured into water. The aqueous mixture is filtered to obtain a solid which is washed sequentially with water, 0.5N hydrochloric acid and water, and dried overnight to give the title product as a beige solid.

Source